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Protein

Pulmonary surfactant-associated protein D

Gene

SFTPD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Contributes to the lung's defense against inhaled microorganisms, organic antigens and toxins. Interacts with compounds such as bacterial lipopolysaccharides, oligosaccharides and fatty acids and modulates leukocyte action in immune response. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties.1 Publication

Miscellaneous

Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB
  • identical protein binding Source: Ensembl

GO - Biological processi

  • cellular protein metabolic process Source: Reactome
  • defense response to bacterium Source: UniProtKB
  • induction of bacterial agglutination Source: AgBase
  • innate immune response Source: UniProtKB
  • lung alveolus development Source: UniProtKB
  • macrophage chemotaxis Source: UniProtKB
  • negative regulation by host of symbiont molecular function Source: AgBase
  • negative regulation of interleukin-2 biosynthetic process Source: UniProtKB
  • negative regulation of T cell proliferation Source: UniProtKB
  • positive regulation of phagocytosis Source: UniProtKB
  • reactive oxygen species metabolic process Source: UniProtKB
  • receptor-mediated endocytosis Source: UniProtKB
  • regulation of adhesion of symbiont to host epithelial cell Source: AgBase
  • regulation of cytokine production Source: UniProtKB
  • regulation of immune response Source: Reactome
  • respiratory gaseous exchange Source: UniProtKB-KW
  • surfactant homeostasis Source: UniProtKB
  • toll-like receptor signaling pathway Source: Reactome

Keywordsi

Biological processGaseous exchange, Immunity, Innate immunity
LigandCalcium, Lectin

Enzyme and pathway databases

ReactomeiR-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-391160 Signal regulatory protein family interactions
R-HSA-5683826 Surfactant metabolism
R-HSA-5686938 Regulation of TLR by endogenous ligand
R-HSA-5687868 Defective SFTPA2 causes idiopathic pulmonary fibrosis (IPF)
R-HSA-5688849 Defective CSF2RB causes pulmonary surfactant metabolism dysfunction 5 (SMDP5)
R-HSA-5688890 Defective CSF2RA causes pulmonary surfactant metabolism dysfunction 4 (SMDP4)
SIGNORiP35247

Protein family/group databases

UniLectiniP35247

Names & Taxonomyi

Protein namesi
Recommended name:
Pulmonary surfactant-associated protein D
Short name:
PSP-D
Short name:
SP-D
Alternative name(s):
Collectin-7
Lung surfactant protein D
Gene namesi
Name:SFTPD
Synonyms:COLEC7, PSPD, SFTP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000133661.15
HGNCiHGNC:10803 SFTPD
MIMi178635 gene
neXtProtiNX_P35247

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted, Surface film

Pathology & Biotechi

Organism-specific databases

DisGeNETi6441
OpenTargetsiENSG00000133661
PharmGKBiPA35715

Chemistry databases

ChEMBLiCHEMBL2176857
DrugBankiDB02379 Beta-D-Glucose

Polymorphism and mutation databases

BioMutaiSFTPD
DMDMi317373510

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20By similarityAdd BLAST20
ChainiPRO_000001746521 – 375Pulmonary surfactant-associated protein DAdd BLAST355

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei35S-nitrosocysteineBy similarity1
Modified residuei40S-nitrosocysteineBy similarity1
Modified residuei784-hydroxyprolineBy similarity1
Modified residuei875-hydroxylysineBy similarity1
Glycosylationi90N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei964-hydroxyprolineBy similarity1
Modified residuei995-hydroxylysineBy similarity1
Modified residuei1714-hydroxyprolineBy similarity1
Modified residuei1774-hydroxyprolineBy similarity1
Disulfide bondi281 ↔ 373
Disulfide bondi351 ↔ 365

Post-translational modificationi

The N-terminus is blocked.
Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.By similarity
S-nitrosylation at Cys-35 and Cys-40 alters the quaternary structure which results in a pro-inflammatory chemoattractive signaling activity with macrophages.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation, S-nitrosylation

Proteomic databases

EPDiP35247
PaxDbiP35247
PeptideAtlasiP35247
PRIDEiP35247
ProteomicsDBi55012

PTM databases

iPTMnetiP35247
PhosphoSitePlusiP35247

Expressioni

Tissue specificityi

Expressed in lung, brain, pancreas and adipose tissue (mainly mature adipocytes).1 Publication

Gene expression databases

BgeeiENSG00000133661
CleanExiHS_SFTPD
ExpressionAtlasiP35247 baseline and differential
GenevisibleiP35247 HS

Organism-specific databases

HPAiCAB004578
HPA044582
HPA056768

Interactioni

Subunit structurei

Oligomeric complex of 4 set of homotrimers.

Binary interactionsi

WithEntry#Exp.IntActNotes
UPK1AO003223EBI-11316157,EBI-14031976

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112339, 4 interactors
IntActiP35247, 3 interactors
STRINGi9606.ENSP00000361366

Structurei

Secondary structure

1375
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi226 – 253Combined sources28
Turni254 – 256Combined sources3
Beta strandi257 – 260Combined sources4
Beta strandi263 – 273Combined sources11
Helixi274 – 283Combined sources10
Beta strandi286 – 288Combined sources3
Helixi294 – 307Combined sources14
Beta strandi311 – 316Combined sources6
Beta strandi318 – 320Combined sources3
Beta strandi323 – 325Combined sources3
Helixi345 – 347Combined sources3
Beta strandi351 – 354Combined sources4
Beta strandi360 – 363Combined sources4
Beta strandi367 – 375Combined sources9

3D structure databases

ProteinModelPortaliP35247
SMRiP35247
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35247

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 222Collagen-likeAdd BLAST177
Domaini260 – 375C-type lectinPROSITE-ProRule annotationAdd BLAST116

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili223 – 252Sequence analysisAdd BLAST30

Sequence similaritiesi

Belongs to the SFTPD family.Curated

Keywords - Domaini

Coiled coil, Collagen, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IS48 Eukaryota
ENOG4110NRD LUCA
GeneTreeiENSGT00700000104102
HOVERGENiHBG108270
InParanoidiP35247
KOiK10068
OMAiAENCVEI
OrthoDBiEOG091G0MYV
PhylomeDBiP35247
TreeFamiTF330481

Family and domain databases

CDDicd03591 CLECT_collectin_like, 1 hit
Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR018378 C-type_lectin_CS
IPR008160 Collagen
IPR033990 Collectin_CTLD
IPR016187 CTDL_fold
IPR015097 Surfac_D-trimer
PfamiView protein in Pfam
PF01391 Collagen, 2 hits
PF00059 Lectin_C, 1 hit
PF09006 Surfac_D-trimer, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SUPFAMiSSF56436 SSF56436, 1 hit
PROSITEiView protein in PROSITE
PS00615 C_TYPE_LECTIN_1, 1 hit
PS50041 C_TYPE_LECTIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P35247-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLFLLSALV LLTQPLGYLE AEMKTYSHRT MPSACTLVMC SSVESGLPGR
60 70 80 90 100
DGRDGREGPR GEKGDPGLPG AAGQAGMPGQ AGPVGPKGDN GSVGEPGPKG
110 120 130 140 150
DTGPSGPPGP PGVPGPAGRE GPLGKQGNIG PQGKPGPKGE AGPKGEVGAP
160 170 180 190 200
GMQGSAGARG LAGPKGERGV PGERGVPGNT GAAGSAGAMG PQGSPGARGP
210 220 230 240 250
PGLKGDKGIP GDKGAKGESG LPDVASLRQQ VEALQGQVQH LQAAFSQYKK
260 270 280 290 300
VELFPNGQSV GEKIFKTAGF VKPFTEAQLL CTQAGGQLAS PRSAAENAAL
310 320 330 340 350
QQLVVAKNEA AFLSMTDSKT EGKFTYPTGE SLVYSNWAPG EPNDDGGSED
360 370
CVEIFTNGKW NDRACGEKRL VVCEF
Length:375
Mass (Da):37,728
Last modified:January 11, 2011 - v3
Checksum:i298917699FC40F6A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22E → G in AAH22318 (PubMed:15489334).Curated1
Sequence conflicti59P → F AA sequence (PubMed:8424457).Curated1
Sequence conflicti122P → A in AAB59450 (PubMed:8428971).Curated1
Sequence conflicti240H → P AA sequence (PubMed:8424457).Curated1
Sequence conflicti341E → K in AAH22318 (PubMed:15489334).Curated1
Sequence conflicti369R → S in CAG46746 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02093731M → T4 PublicationsCorresponds to variant dbSNP:rs721917EnsemblClinVar.1
Natural variantiVAR_020938123L → V2 PublicationsCorresponds to variant dbSNP:rs17878336EnsemblClinVar.1
Natural variantiVAR_020939180T → A4 PublicationsCorresponds to variant dbSNP:rs2243639EnsemblClinVar.1
Natural variantiVAR_020940290S → T2 PublicationsCorresponds to variant dbSNP:rs3088308EnsemblClinVar.1
Natural variantiVAR_020941309E → K1 PublicationCorresponds to variant dbSNP:rs4469829EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X65018 mRNA Translation: CAA46152.1
L05485, L05483, L05484 Genomic DNA Translation: AAB59450.1
CR541948 mRNA Translation: CAG46746.1
AY216721 Genomic DNA Translation: AAO22991.1
AL512662 Genomic DNA No translation available.
BC022318 mRNA Translation: AAH22318.1
CCDSiCCDS7362.1
PIRiA45225
RefSeqiNP_003010.4, NM_003019.4
XP_011538389.1, XM_011540087.1
UniGeneiHs.253495

Genome annotation databases

EnsembliENST00000372292; ENSP00000361366; ENSG00000133661
GeneIDi6441
KEGGihsa:6441
UCSCiuc001kbh.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSFTPD_HUMAN
AccessioniPrimary (citable) accession number: P35247
Secondary accession number(s): Q5T0M3
, Q6FH08, Q86YK9, Q8TCD8, Q9UCJ2, Q9UCJ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 11, 2011
Last modified: July 18, 2018
This is version 195 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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